Clinical Trial: MVA-BN®-Filo and Ad26.ZEBOV Vaccines in Healthy Volunteers

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: A Phase I Trial to Utilize Systems Biology Approaches to Examine the Safety, Immunogenicity, and 'Omics Response to MVA-BN®-Filo and Ad26.ZEBOV Vaccines in Healthy Volunteers

Brief Summary: This is a Phase 1, double-blind, randomized trial to evaluate the safety and immunogenicity of two heterologous and two homologous prime-boost regimens using MVA-BN®-Filo and Ad26.ZEBOV administered in different sequences at Days 1 and 29 in healthy adult subjects aged 18 - 45 years.The study will evaluate the 'omics (transcriptomics, proteomics, lipidomics, metabolomics), antibodies for immunogenicity, CMI, ADCC, lymphoproliferative and plasmablast responses to MVA-BN®-Filo and Ad26.ZEBOV vaccines. The primary objectives of this study are: 1) To Assess the safety and reactogenicity of each study group. 2) To assess responses to the study vaccination by study group after the first, second and third dose by transcriptomics. 3) To assess the peak antibody response to the study vaccination by study group to filovirus antigens.

Detailed Summary: This is a Phase 1, double-blind, randomized trial to evaluate the safety and immunogenicity of two heterologous and two homologous prime-boost regimens using MVA-BN®-Filo and Ad26.ZEBOV administered in different sequences at Days 1 and 29 in healthy adult subjects aged 18 - 45 years. The two heterologous prime-boost groups will also receive MVA-BN®-Filo at day 366. Sixty subjects will be randomized 1:1:1:1 to one of four study groups (15 per group).Subjects and study staff will be blinded to a subject's study vaccine assignment within study vaccination schedule (e.g., enrollment into Group 1 or 4 versus 2 or 3 will be known). The study will evaluate the 'omics (transcriptomics, proteomics, lipidomics, metabolomics), antibodies for immunogenicity, CMI, ADCC, lymphoproliferative and plasmablast responses to MVA-BN®-Filo and Ad26.ZEBOV vaccines. The primary objectives of this study are: 1) To Assess the safety and reactogenicity of each study group. 2) To assess responses to the study vaccination by study group after the first, second and third dose by transcriptomics. 3) To assess the peak antibody response to the study vaccination by study group to filovirus antigens. Secondary objectives are: 1) To assess antigen-specific cell-mediated immune (CMI) responses to the study vaccination by study group.2) To Assess antibody-dependent cell-mediated cytotoxicity (ADCC) responses to the study vaccination by study group.
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Current Primary Outcome:

  • Determine the differential expression from baseline in mRNA after each study vaccination by study group [ Time Frame: Screening and Days 1, 2, 4, 8, 15, 29, 30, 32, 36, 43, and 57 for Groups 1 and 4; additionally Days 366, 367, 369, 373, 380, 394, and 546 for Groups 2 and 3. ]
  • Determine the number of subjects with a vaccine-related serious adverse event (SAE) from the time of first study vaccination by study group through the duration of the study [ Time Frame: Day 1 through Day 366 in Groups 1 and 4; Day 1 through Day 546 in Groups 2 and 3 ]
  • Determine the number of subjects with a vaccine-related unsolicited adverse event (AE) from the time of each study vaccination by study group [ Time Frame: Day 1 through Day 29 ]
  • Determine the number of subjects with solicited local and systemic reactogenicity events from the time of study vaccination by study group. [ Time Frame: Day 1 through Day 8 ]
  • Determine the peak antibody response against filovirus glycoproteins (GPs) for each study group [ Time Frame: Days 1, 15, 29, 36, 43, 57, 209, and 366 for Groups 1 and 4; additionally Days 369, 373, 380, 394, 546 for Groups 2 and 3. ]


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Determine the change in CMI response from baseline against filovirus antigen using peptide pools and measurement by intracellular cytokine staining (ICS) in each of the study groups [ Time Frame: Days 1, 15, 29, 36, 43, 57, 209, and 366 in Groups 1 and 4; additionally Days 369, 373, 380, 394, and 546 in Groups 2 and 3. ]
  • Determine the change in the ADCC from baseline in each of the study groups [ Time Frame: Days 1, 15, 29, 36, 43, 57, 209, and 366 for Groups 1 and 4; additionally Days 373, 380, 394, and 546 for Groups 2 and 3. ]


Original Secondary Outcome:

  • Determine the change in the ADCC from baseline in each of the study groups [ Time Frame: Days 1, 15, 29, 36, 43, 57, 209, and 366 for Groups 1 and 4; additionally Days 373, 380, 394, and 546 for Groups 2 and 3. ]
  • Determine the change in CMI response from baseline against filovirus antigen using peptide pools and measurement by intracellular cytokine staining (ICS) in each of the study groups [ Time Frame: Days 1, 15, 29, 36, 43, 57, 209, and 366 in Groups 1 and 4; additionally Days 369, 373, 380, 394, and 546 in Groups 2 and 3. ]


Information By: National Institute of Allergy and Infectious Diseases (NIAID)

Dates:
Date Received: September 1, 2016
Date Started:
Date Completion:
Last Updated: January 26, 2017
Last Verified: July 25, 2016